The present invention relates to 4-benzyl-2-hydroxy-1,4-oxazin-3-one which is useful as an intermediate in the preparation of certain therapeutic agents. In particular, the present invention provides 4-benzyl-2-hydroxy-1,4-oxazin-3-one which is an intermediate in the synthesis of pharmaceutical compounds which are substance P (neurokinin-1) receptor antagonists.
General processes are disclosed in the art for the preparation of compounds related to 4-benzyl-2-hydroxy-1,4-oxazin-3-one, but these result in relatively low and inconsistent yields of the desired product (A. Le Rouzic-Bleeevre, Fr. C. R. Hebd. Seances Acad. Sci., Ser. C., 282 (6) 307-310 (1976); T. Mancilla, et al., Heteroatom. Chem., 6(6) 605-609 (1995)). In contrast to the previously known processes, the present invention provides effective methodology for the preparation of 4-benzyl-2-hydroxy-1,4-oxazin-3-one in relatively high yield and purity.
It will be appreciated that 4-benzyl-2-hydroxy-1,4-oxazin-3-one is an important intermediate for a particularly useful class of therapeutic agents. As such, there is a need for the development of a process for the preparation of 4-benzyl-2-hydroxy-1,4-oxazin-3-one which is readily amenable to scale-up, uses cost-effective and readily available reagents and which is therefore capable of practical application to large scale manufacture.
Accordingly, the subject invention provides 4-benzyl-2-hydroxy-1,4-oxazin-3-one via a very simple, short, relatively inexpensive and highly efficient synthesis.
This invention is directed to the compound 4-benzyl-2-hydroxy-1,4-oxazin-3-one of the formula: 
This compound is an intermediate in the synthesis of compounds which possess pharmacological activity. In particular, such compounds are substance P (neurokinin-1) receptor antagonists which are useful e.g., in the treatment of psychiatric disorders, inflammatory diseases, and emesis.